The safety of bivalirudin during elective percutaneous coronary interventions in heart transplant patients

Background: Bivalirudin has been shown to be safe and effective during percutaneous coronary interventions (PCI) of native coronary arteries in the REPLACE 2 trial. The safety of bivalirudin during PCIs in heart transplant patients is not known. Methods: Heart transplant patients who had undergone PCI of de novo lesions and received bivalirudin during the procedure were included in the study. Medical records were reviewed for the occurrence of death, myocardial infarction, target vessel revascularization or major bleeding up to 30 days after discharge. The results were compared with the REPLACE 2 trial and with a control group of heart transplant recipients who received heparin during their procedures. Results: There were 51 separate PCIs performed in 30 patients in the study group. The mean age was 56 ± 12 years and 6 (20%) were women. The control group consisted of 24 patients who had undergone 35 PCIs. There were no deaths, myocardial infarctions or target vessel revascularization during the follow-up period in the study group. The combined endpoint of death, myocardial infarctions, target vessel revascularization and major bleeding requiring two or more units of packed red blood cells occurred in 2 (3.9%) patients compared to 275 (9.2%) patients in the REPLACE 2 trial (p = 0.195) and 5 (14.3%) in the control group (p = 0.115). Conclusion: Bivalirudin is a safe antithrombotic medication to use during elective PCI in heart transplant patients with cardiac allograft vasculopathy. (Cardiol J 2007; 14: 458-462

Bezpieczeństwo stosowania biwalirudyny podczas elektywnych przezskórnych interwencji wieńcowych u pacjentów po przeszczepie serca

Wstęp: W badaniu REPLACE 2 wykazano zarówno bezpieczeństwo, jak i skuteczność stosowania biwalirudyny podczas przezskórnych interwencji wieńcowych (PCI) dotyczących natywnych tętnic wieńcowych. Nie istnieją natomiast doniesienia na temat bezpieczeństwa zastosowania biwalirudyny w trakcie PCI u pacjentów po przeszczepie serca. Metody: Do badania włączono chorych po zabiegu transplantacji serca, u których wykrywane de novo zmiany w naczyniach wieńcowych zaopatrywano na drodze PCI. Za punkt końcowy badania uznano wystąpienie w ciągu 30 dni po zabiegu: zgonu pacjenta, zawału serca, konieczności wykonania rewaskularyzacji dotyczącej zaopatrywanego wcześniej na drodze PCI naczynia oraz poważnego krwawienia. Wyniki badania porównano zarówno z rezultatami REPLACE 2, jak i z wynikami uzyskanymi w grupie kontrolnej (pacjenci po przeszczepie serca otrzymujący podczas procedur PCI heparynę). Wyniki: W grupie badawczej wykonano 51 zabiegów PCI u 30 chorych. Średnia wieku w tej grupie wynosiła 56 ± 12 lat; kobiety stanowiły 20% ogółu grupy. Grupa kontrolna składała się z 24 chorych, u których wykonano 35 zabiegów PCI. W grupie badawczej podczas okresu obserwacji nie stwierdzono wystąpienia: zgonu, zawału serca lub konieczności rewaskularyzacji naczynia wieńcowego zaopatrywanego wcześniej za pomocą PCI. Złożony punkt końcowy w postaci: zgonu, zawału serca, konieczności rewaskularyzacji naczynia wieńcowego zaopatrywanego wcześniej za pomocą PCI oraz poważnego krwawienia wymagającego przetoczenia przynajmniej 2 j. koncentratu krwinek czerwonych wystąpił u 2 (3,9%) chorych w porównaniu z 275 (9,2%) pacjentami w badaniu REPLACE 2 (p = 0,195) oraz 5 (14,3%) osobami w grupie kontrolnej (p = 0,115). Wnioski: Biwalirudynę, lek o działaniu przeciwzakrzepowym, można bezpiecznie stosować w przebiegu elektywnej PCI wykonywanej u pacjentów z waskulopatią w przeszczepionym sercu. (Folia Cardiologica Excerpta 2008; 3: 29-34

Angiotensin II Modulates Catecholamine Release Into Interstitial Fluid of Canine Myocardium in Vivo

This study tested the hypothesis that exogenous infusion of angiotensin II (ANG II) leads to the release of catecholamines [norepinephrine (NE) and epinephrine (EPI)] into the cardiac interstitial fluid (ISF) space of dogs with adrenals intact (AI) (n = 7) and with adrenals clamped (AC) (n = 5). LV ISF samples were collected at 3-min intervals during administration of ANG II (100 μM ANG II at 1 ml/min for 10 min) to right atrial neurons via their local arterial blood supply and during electrical stimulation of the stellate ganglia of open-chest anesthetized dogs. In AI dogs, ANG II caused ISF NE to increase fivefold (P \u3c 0.05) without a significant increase in coronary sinus (CS) NE. Electrical stimulation (5 ms, 4 Hz, 8-14 V, and 10 min) of the stellate ganglia caused a similar increase in ISF NE (P \u3c 0.05), accompanied by a sevenfold increase in CS NE (P \u3c 0.05). ISF EPI increased greater than sixfold during ANG II infusion (P \u3c 0.05) and during stellate stimulation. However, during ANG II infusions, aorta plasma EPI levels increased fourfold in AI dogs, whereas in AC dogs, CS NE and EPI levels were unaffected during ANG II infusions. Nevertheless, baseline ISF NE and EPI did not differ and increased to a similar extent during ANG II infusions in AI versus AC dogs. Thus exogenously administered ANG II increases the amount of NE liberated into the ISF independent of the adrenal contribution, the amount matching that induced by electrical stimulation of all cardiac sympathetic efferent neurons. In contrast, NE spillover into the CS occurred only during electrical stimulation of stellate ganglia. NE release and uptake mechanisms within the myocardium are differently affected, depending on how the final common pathway of the sympathetic efferent nervous system is modified

Β\u3csub\u3e1\u3c/sub\u3e-Adrenergic Receptor Blockade Attenuates Angiotensin II-Mediated Catecholamine Release Into the Cardiac Interstitium in Mitral Regurgitation

Background - This study tested the hypothesis that β1-adrenoreceptor blockade modulates the angiotensin II (Ang II)-evoked neural release of norepinephrine (NE) and epinephrine (Epi) into the cardiac interstitial fluid (ISF) space in experimentally induced mitral regurgitation (MR) in the dog. Methods and Results - Normal dogs (n=8) were compared with dogs with MR of 2 (n=8) and 4 (n=6) weeks\u27 duration and with dogs with MR treated with β1-receptor blockade (RB; extended-release metoprolol succinate, 100 mg QD; MR+β1-RB) that was started 24 hours after MR induction for 2 (n=6) and 4 weeks (n=8). Left ventricular end-diastolic dimension increased 20% as plasma Ang II levels increased \u3e5-fold in both MR and MR+β1-RB dogs at 2 and 4 weeks. Ang II infusion into the left atrium produced increases in ISF NE and Epi in normal dogs, which were further increased in 2- and 4-week MR dogs but were restored to normal in 4-week MR+β1-RB dogs. Ang II infusion produced 4-fold increases in circulating NE and Epi in 2- and 4-week MR dogs that returned to normal in 4-week+β1-RB dogs. Left ventricular angiotensin-converting enzyme activity and ISF Ang II were increased in 4-week MR dogs but were decreased in 4-week MR+β1-RB dogs. Conclusions - β1-RB decreases renin-angiotensin system sympathostimulation and activation by attenuating the Ang II-mediated NE and Epi release into the cardiac ISF and circulation and by decreasing left ventricular angiotensin-converting enzyme expression in the early phases of volume overload

Β\u3csub\u3e1\u3c/sub\u3e-Adrenoceptor Blockade Mitigates Excessive Norepinephrine Release Into Cardiac Interstitium in Mitral Regurgitation in Dog

Mitral regurgitation (MR) is associated with increased neuronal release of norepinephrine (NE) and epinephrine (EP) into myocardial interstitial fluid (ISF) that may be necessary in sustaining left ventricular (LV) function via activation of cardiomyocyte β-adrenergic receptors (ARs). However, activation of neuronal β-ARs on cardiac neurons may lead to further catecholamine release, with an attendant risk of functional deterioration. We hypothesize that a beneficial effect of β-AR blockade may therefore mitigate excessive catecholamine release from cardiac adrenergic neurons in dogs with MR. We measured the effects of chronic β-receptor blockade (β-RB) on ISF NE and EP release using in vivo microdialysis in open-chest anesthetized dogs after 4 wk of MR with or without extended release of metoprolol succinate (100 mg/day) as well as in control dogs. Fractional shortening increased by 30% in both MR and MR + β-RB dogs after 4 wk of MR. In MR + β-RB dogs, stellate-stimulated heart rate change was attenuated compared with control and MR dogs, whereas peak change of LV pressure over time (+dP/dt) increased equally in all groups. Stellate-stimulated ISF NE increased fivefold over baseline in MR versus twofold in control dogs (\u3c0.05), but the NE release was significantly attenuated in MR + β-RB dogs. In contrast, stellate-stimulated increases in ISF EP did not differ in control, MR, and MR + β-RB dogs. This study demonstrates that β-RB attenuates ISF NE release from cardiac neurons and that the LV functional response to MR is not dependent on an excess increase in ISF NE. Thus β1-RB may exert a beneficial effect by attenuating untoward effects of excessive sympathetic efferent neural NE release while sustaining early LV functional adaptation to MR